Preparation of 1-(carbamoyl)-n-(carbamoyloxy)-thioformimidates from acetoacetamides

ABSTRACT

1-(Carbamoyl)-N-(carbamoyloxy)thioformimidates such as methyl 1(carbamoyl)-N-methylcarbamoyloxy)thioformimidate and methyl 1(dimethylcarbamoyl)-N-(methylcarbamoyloxy)thioformimidate are prepared by the steps of A. REACTING DIKETENE WITH AMMONIA OR AN AMINE TO OBTAIN AN ACETOACETAMIDE; B. REACTING THE PRODUCT OF (A) WITH A NITROSATING AGENT IN THE PRESENCE OF WATER OR AN ALCOHOL; C. CHLORINATING THE PRODUCT OF (B) AT A TEMPERATURE OF -10 TO 75* C.; d. reacting the product of (c) with an alkyl mercaptan and a base or with a metal salt of an alkyl mercaptan; and E. REACTING THE PRODUCT OF (D) WITH 1. A CARBAMOYL CHLORIDE IN THE PRESENCE OF A BASE; 2. PHOSGENE FOLLOWED BY REACTION WITH AN AMINE; OR 3. AN ISOCYANATE, OPTIONALLY IN THE PRESENCE OF A BASIC CATALYST; IN WATER OR ORGANIC SOLVENTS SUCH AS ACETONE, METHYLENE CHLORIDE, METHYL ETHYL KETONE, METHYL ISOBUTYL KETONE, DIMETHYLFORMAMIDE, DIMETHYLACETAMIDE, DIMETHYLSULFOXIDE, TETRAMETHYLUREA OR THEIR MIXTURES.

[22] Filed:

United States Patent Fuchs et al.

[S4] PREPARATION OF l-(CARBAMOYL)-N- (CARBAMOYLOXY)- THIOFORMIMIDATES FROM ACETOACETAMIDES [72] Inventors: Julius J. Fuchs, I104 Greenway Road, Wilmington, Del. [9803; Harvey M. Loux, 115 Summerset Drive, Hockessin, Del. 19707 Sept. 16, 1970 [21] Appl. No.: 72,793

Related 0.8. Application Data [63] Continuation-impart of Ser. No. 787,594, Dec.

27, 1968, abandoned.

[52] US. Cl. ..260/239 A, 260/239 BF, 260/239 E, 260/293.86, 260/326.8, 260/326.82, 260/453 R, 260/543 A, 260/543 R, 2601561 K,

7 260/561 HL, 260/999 [51] Int. Cl. ..C07d 29/22 [58] Field of Search ..260/56l K, 561 EL, 293.86, 260/326.8, 239 BF, 239 E, 239 A [151 3,694,431 [451 Sept. 26, 1972 Primary Examiner-Lewis Gotts Assistant Examiner-Ethel G. Love Attorney-Don M. Kerr [57] ABSTRACT l-(Carbamoyl)-N-(carbamoyloxy)thioformimidates such as methyl l-(carbamoyl)-N-methylcarbamoyloxy)thioformimidate and methyl l-(dimethylcarbamoyl)-N-(methylcarbamoyloxy)thioformimidate are prepared by the steps of a. reacting diketene with ammonia or an amine to obtain an acetoacetamide;

b. reacting the product of (a) with a nitrosating agent in the presence of water or an alcohol;

c. chlorinating the product of (b) at a temperature of-l0 to 75 C.;

d. reacting the product of (c) with an alkyl mercaptan and a base or with a metal salt of an alkyl mercaptan; and

e. reacting the product of (d) with l. a carbamoyl chloride in the presence of a base; 2. phosgene followed by reaction with an amine;

3. an isocyanate, optionally in the presence of a basic catalyst; in water or organic solvents such as acetone, methylene chloride, methyl ethyl ketone, methyl isobutyl ketone, dimethylformamide, dimethylacetamide, dimethylsulfoxide, tetramethylurea or their mixtures.

2 Claims, No Drawings PREPARATION OF l-(CARBAMOYU-N- (CARBAMOYLOXfi-Tl-IIOFORMIMIDATES FROM ACETOACETAMIDES CROSS-REFERENCE TO RELATED APPLICATION This application is a continuation-in-part of application Ser. No. 787,594,-filed Dec. 27, 1968, now abandoned.

BACKGROUND OF THE INVENTION This invention relates to methods for preparing l- (carbamoyl)-N-(carbamoyloxy)thioformimidates. More particularly this invention is directed to methods of preparing the thioformimidates by reacting diketene with ammonia or an amine, reacting the product with nitrous acid or other nitrosating agent, chlorinating the product of that reaction, then reacting the chlorination product with an alkyl mercaptan and a base, and then preparing the desired thiofonnimidate by reaction either with a suitable carbamoyl chloride in the presence of a base or with phosgene, followed by reaction with an amine, or with an isocyanate usually in the presence of a basic catalyst.

The product thioformimidates are useful as pesticides and can be prepared in the manner disclosed in copending application Ser. No. 728,739, filed May 13, i968, now U.S. Pat. No. 3,530,220. They can also be prepared from glyoxylic acid in the manner disclosed and claimed in copending application Ser. No. 772,811, filed Nov. 1, 1968, now U.S. Pat. No. 3,584,032.

By the methods of this invention it is possible to prepare the thioformimidates of formula (1) below in a five-step process in which the first four steps or all five steps can beoperatively combined. By thus avoiding the necessity to separate and recover intermediate compounds the methods of this invention permit economic preparation of the compounds of formula l below in outstanding yield.

SUMMARY OF THE INVENTION In summary, this invention is directed to the preparation of l-(carbamoyl)-N-(carbamoyloxy)thioformimidates of the following formula:

wherein v R, is alkyl of one through four carbon atoms or alkenyl of three through four carbon atoms;

R, is hydrogen, alkyl of one through four carbon atoms, methoxy, or cycloalkyl of three through five carbon atoms;

R, is hydrogen or alkyl of one through four carbon atoms; with the proviso that R, and R, can be joined and are alkylene of two through six carbon atoms, and with the limitation that R, and IQ never total more than seven carbon atoms;

R is alkyl of one through three carbon atoms, allyl or propargyl; and r R, is hydrogen or methyl;

2 by the steps comprising:

a. reacting diketene with ammonia or an amine in the presence of water, an inert organic solvent or the product of the reaction itself;

b. reacting the product of (a) with nitrous acid or other nitrosating agents in the presence of water, methanol, ethanol, isopropanol or their mixtures;

c. chlorinating the product of (b) at a temperature of l 0 to C.;

d. reacting the product of (c) with an alkyl mercaptan and a base or with a metal salt of an alkyl mercaptan and reacting the product of (d) with (1) a carbamoyl chloride in the presence of a base; (2) phosgene followed by reaction with an amine; or (3) an isocyanate in the presence or absence of a basic catalyst; in water, acetone, methylene chloride, methyl ethyl ketone, methyl isobutyl ketone,

dimethylformamide, dimethylacetamide, dirnethylsulfoxide, tetramethylurea or their mixtures.

The compounds of formula (1) and their use as pesticides are described and exemplified in Application Ser. No. 728,739, referred to above.

DESCRIPTION OF THE INVENTION The process of this invention used in preparing the compounds of formula (1) comprises the five steps enumerated above, and more fully described as follows: Step a.

The reaction of diketene with ammonia or an amine in the presence of water, an inert organic solvent or the product of the reaction itself,

OHFC-CH: NH

in which R, and R are as defined in formula l above.

Equimolecular quantities of diketene and ammonia or an amine are gradually mixed in a solvent such as diethyl ether, benzene, methylene chloride, or water, with water the preferred solvent. In addition the reaction product itself may be used as the reaction solvent. The use of either reactant, diketene on the one hand or ammonia or an amine on the other, in excess of the stoichiometric amount required is permissible but unnecessary and wasteful. The diketene can be added to a solution of ammonia or amine, or the ammonia or amine can be added to a solution of diketene, or both reactants can be added simultaneously to the solvent. It is preferred to add the diketene to an aqueous solution of ammonia or amine.

The reaction is carried out at a temperature between about 20 C. and C., depending on the solvent used. If water is used as solvent a reaction temperature of between about 0 C. and 50 C. is preferred. The time of addition is not critical and depends upon the cooling capacity of the reaction equipment. For economy and convenience it is preferred to keep addition time to a minimum. Addition times of 30 to 60 minutes are ordinarily adequate. The reaction is complete when a stable pH of 6-8, preferably pH 7.0-8.0, is obtained.

At the conclusion of the reaction the product can be isolated by conventional techniques such as by evaporation of the solvent or extraction with an organic solvent, and can be purified by distillation. However, it is ordinarily preferred to run the step (a) reaction in water, and to use the product in the step (b) nitrosation without isolation of the step (a) product.

Step b.

The nitrosation of the acetoacetamide is represented by the following equation wherein R and R are as defined above and R is hydrogen or alkyl of one to five carbon atoms.

The acetoacetamide and solvent, if not already present from step (a), are charged initially to the reaction vessel. The nitrosating agent is then added as a solid, a liquid, a vapor, or in solution, at a rate such that a reaction temperature between l C. and 70 C. is maintained. If a metal nitrite is to be used in conjunction with an acid as a nitrosating agent, by generating nitrous acid, the metal nitrite is added to the reaction mixture as rapidly as is convenient, either as a solid or in solution. Then the acid is added at such a rate that the temperature remains between l0 C. and 70 C. and preferably between 0 C. and 35 C. The addition rate of the acid is also controlled so that the pH of the reaction mixture does not go below about 4.0 until about 80 percent of the stoichiometric quantity of acid has been added, based on the amount of metal nitrite used. A final pH of 2.0- 2.5 is attained when the stoichiometric quantity of acid has been added. If the acid is added at a rate so rapid that the pH and temperature control are not maintained, nitrous acid may be liberated too rapidly and enter into undesirable side reactions.

Water, methanol, ethanol, isopropanol and their mixtures are suitable solvents. Of these, water is generally the preferred solvent for reasons of economy and solubility. If step (c) is to be carried out without isolation of the product of this step it is of added importance that this step be carried out in water because of the tendency of some organic solvents to chlorinate under the conditions of step (c).

Suitable nitrosating agents are dinitrogen trioxide; alkyl nitrites; and sodium nitrite, potassium nitrite, and calcium nitrite used in conjunction with an acid such as hydrochloric, sulfuric or acetic. Of these, sodium nitrite in conjunction with hydrochloric acid is the preferred source of nitrous acid because of convenience and economy and ease of handling the byproduct sodium chloride.

As stated above, water is the preferred solvent and it is preferred to use water in an amount of about 0.4 liters per mole of the acetoacetamide. Thus when sodium nitrite and hydrochloric acid, the preferred source of nitrous acid, are used to generate nitrous acid the sodium chloride by-product remains in solution, facilitating handling of the reaction mixture.

The nitrosating agent is used in l to 5 percent excess over the stoichiometric amount based on the acetoacetamide. Greater or lesser amounts can be used but only at an economic disadvantage.

When an acid is used in conjunction with a metal nitrite, it is used in stoichiometric amounts based on the source of nitrous acid. Use of amounts greater or less than stoichiometric results in waste of one of the reactants.

If desired the product of step (b) can be isolated, such as by filtration or extraction with an organic solvent. However as stated above, when the solvent is water it is preferred to go directly to step (0) without isolating the product of step (b).

Step c.

Step (c) comprises formation of the hydroxamoyl chloride and is illustrated by the equation:

OH Rs ROH I C]:

wherein R is hydrogen, methyl, ethyl, or isopropyl.

If the intermediate product of step (b) has been isolated or purified, it is preferred to mix the product with water, cool the mixture and add chlorine. If the step (b) product has not been isolated from the reaction medium of step (b) the product mixture is cooled and chlorinated as is.

The chlorination should be carried out at a temperature between 10 C. and C. and preferably between 20 C. and 50 C. The amount of chlorine used will vary from stoichiometric to 5 percent molar excess but it is preferred to use stoichiometric amounts.

The chlorine is ordinarily added over a period of 30 to 60 minutes although it can beadded more rapidly if desired. After addition is complete the mixture is stirred, usually for about 30 to 60 minutes, usually at a temperature of about 20 to 50 C. The reaction is complete when no further chlorine is absorbed.

Elemental chlorine is the preferred source of chlorine for economic reasons, however other chlorinating agents, such as sulfuryl chloride, can be used if desired.

Suitable solvents include water, methanol, ethanol, isopropanol, their mixtures, or their mixtures with dimethylforrnamide. For economic reasons water is the preferred solvent and obviously when step (b) product is used without isolating the product from the solvent, step (c) is carried out in the solvent of step (b).

The reaction product of step (c) which crystallizes out during the chlorination in water solution can be isolated, if desired, in high yield and purity by filtration, or it can be used directly without isolation in the reaction of step d). It is preferred to isolate the product of step (0) before the reaction of step (d) because such a procedure improves the purity of the step (d) product, improves the ease of operation of step (d), and reduces consumption of the base in step (d).

Step (d) The hydroxamoyl chloride from step (c) is reacted with an alkyl mercaptan and a base in a solvent according to the equation:

O N-OH N- SR1 i JCl RISK base Ra Ba mercaptan. An aqueous solution of base is then added to accept the HCl liberated during the reaction. This procedure is preferably carried out in methanol as a solvent. The product can be isolated by removing the low boiling solvent by distillation, adding water to the distillation pot as necessary to maintain a practical slurry concentration, followed by filtration. 2) The hydroxamoyl chloride in the reaction medium of step (c) is treated with a pre-prepared solution of a metal salt of an alkyl mercaptan or with the alkyl mercaptan, followed by addition of the aqueous base. More base is required for this procedure than in 1) above because of I the additional acetic acid and hydrochloric acid which are present in the reaction mixture of step (c). The

product can be isolated by simple filtration if desired.

Bases which are suitable acid acceptors for adjusting the pH are the hydroxides, carbonates and bicarbonates of sodium, potassium, calcium and magnesium. The final pH should be between 5 and 9 and a pH of about 7 is preferred.

As stated, the product can be isolated if desired, or alternatively, if water or dimethylformamide is the solvent, the product mixture can be used as is in step (e). It is usually preferred to isolate the product prior to use in step (e).

Step e.

Conversion of the product of step (d) to the desired formimidate is carried out by reacting the product of step (d) with an isocyanate, or carbamoyl chloride, or phosgene followed by reaction with an amine, according to the equation vtl ereislea ia r and R4 r ee ss above or wherein R R R R and R are as defined above.

The reactions of step (e) are carried out in a solvent such as water, acetone, methyl ethyl ketone, methyl isobutyl ketone, dimethylformamide, dimethylacetamide, tetramethylurea, dimethylsulfoxide, methylene chloride, or their mixtures, at a temperature which can range from below l0 C. to about 55 C. At substantially higher temperatures the products exhibit instability. Anhydrous solvents are preferred to avoid possible side-reactions of isocyanate or carbamoyl chloride with water. The reaction of step (e,) is facilitated by the presence of a basic catalyst such as trimethylamine, triethylamine or triethylenediamine. The reaction of step (e;) is carried out in the presence of an equimolar quantity of a base such as triethylamine, trimethylamine or the hydroxides, carbonates or bicarbonates of sodium, potassium, calcium or magnesium. Alternatively, the sodium salt of the product of step (d) can be formed by reaction with a metal hydride such as sodium hydride. The resulting sodium salt can then be reacted with a carbamoyl chloride in an inert solvent such as tetrahydrofuran to obtain products as obtained in the (c reaction.

The reactions of step (e;,) may be carried out in any of several different ways, for example:

1. The sodium salt of the product of step (d) can be formed by reaction with a metal hydride such as sodium hydride. The resulting sodium salt can be reacted with phosgene in an inert solvent such as tetrahydrofuran followed by reaction with the desired amine,

, and an acid acceptor such as a tertiary amine or a hydroxide, carbonate or bicarbonate of sodium, potassium, calcium and magnesium. The amine itself maybe used as the acid acceptor in which event two moles of amine are used.

2. To a solution of a product of step (d) and phosgene in an inert solvent sodium hydroxide is added followed by reaction with the desired amine (R R NH) and an acid acceptor or, as above, two molar portions of the amine may be used with no other acid acceptor needed.

3. To a solution of the product of step (d) and phosgene in an inert solvent three molar portions of the desired amine can be added.

The l-(carbarnoyl)-N-(carbamoyloxy)thioformimidate products of step (e) can be isolated by conventional procedures such as filtration or extraction or may be used in solution as prepared, depending upon the solvent chosen.

Of the steps (a) through (e) the more important are tained. The reaction product starts to crystallize Steps and and the most impomlm is p toward the end of the caustic addition. 5 The which Provides an advantageous method of Preparing methanol is removed from the resulting slurry by the chlorinated intermediate. A preferred sequence of di il i il a head temperature f C. at reaction is to nitrosate and chlorinate in step (b) and 5 mm is obtained; this operation removes the reaaions, 3 Previously Obtained acetoacetamlde methanol and excess methyl mercaptan. The aque- P P by any Suitable process step and follow ous slurry is then cooled to 0C. and the methyl 1- the chlorination the steps (e). 7 As will be evident to those skilled in the art, the steps I 0 of this process can be operated separately or together in a continuous manner without departing from the concept of this invention. 7

The process of this invention is further illustrated in the following examples wherein parts and percentages are by weight unless otherwise noted.

(dimethylcarbamoyl)-N-hydroxythioformimidate isolated by filtration. After one washing with ice water, and drying, there is obtained 36.5 parts of methyl l-(dimethylcarbamoyl )-N-hydroxythioformimidate, melting point l83-l84 C.

b) One half of the slurry of dimethylcarbamoylformhydroxamoyl chloride obtained above is cooled to 0C. and 14 parts of methyl mercaptan added, followed by the gradual addition of 60 parts of 50 percent aqueous u...u.. sodium hydroxide solution at 0 to C. until a stable To 86 p of a 25 percent aqueous Solution of pH of 7 is obtained. The resulting reaction mixture is dimethylamine is added 200 parts of water, followed by h Pooled to lo P the sohqs fihefed Washed the addition of enough diketene at 20 to 30C. to give wlth water 0 dned- There Obtamed 34 pa of a stable pH of 7; 41.3 parts of diketene are required. To s f y g y ly y the resulting solution is then added 35 parts of sodium f l t melting P9 172 one y i i f ll ed b h d l dditi f 50 parts f hzation frpm water gives a pure product, melting pomt 36 percent aqueous hydrochloric acid under nitrogen atmosphere at C. so that the pH of the solution T0 8 p n l n 0f 70 parts of methyl l-(dimethylremains above 4.5 throughout the addition of the first carbamoyl)-N-hydroxythioformimidate and A part of 40 parts of acid. The 2-hydroxyimino-N,N- 3o triethylenediamine in 350 parts of acetone at 40 C. is dimethylacetoacetamide crystallizes toward the end of added slowly 27 parts of methyl isocyanate. The temthe hydrochloric acid addition. To the resulting reacperature of the reaction mass rises to 58 C. After the tion mixture is then added at 30C. within 45 to 60 temperature of the reaction mass has subsided to 25 minutes 36 parts of chlorine. After agitation for an ad- 0, the solvent is evaporated under reduced pressure to ditional 1% hour, the resulting slurry of dimethylcarobtain a crystalline residue. Recrystallization of the bamoylformhydroxamoyl chloride is split into two residue from benzene gives one crystalline form of batches and converted in two different ways to the methyl 1-(dimethylcarbamoyl)-N-(methylcarmethyl l-(dimethylcarbamoyl)-N-hydroxythioforbamoyloxy)thioformimidate, melting point 109-110 mimidate,asdescribed below: C. Recrystallization from water gives another crystala. one half of the slurry obtained above is cooled to li form of methyl l-(dimethylcarbamoyl)-N-(methyll0 C. and the Solids a isolated y filtrationcarbamoyloxy)thioformimidate, melting point l0l10 After a washing with ice water, the wet solids are 3 C. dissolved in 150 parts of methanol at 30 C. To this The compounds of Table I are prepared by the solution is then added 16 parts of methyl mercapprocedures of Example I, using the mercaptans, amines tan, followed by the addition at 30 C. of 20 parts and isocyanates listed in place of the methyl mercapof percent aqueous sodium hydroxide solution tan, dimethylamine and methyl isocyanate of Example in 1 50 parts of water until a stable pH of is obl;

TABLE I Mercapt-an Amine Isocyanate Product u D th Lmine Methyl isocya at Ethyl -(di e hylcarbamoyl)- -(methylcurbnmoyloxy)thloformimid te, E 3 do Allyll-(dimethylcarbumoyl)-N-( 0t y 08 8 y Y) 1 mercaptan do Ethyl isocyanate B t gyl1-(dimethylcarbamoyl)-N-(ethylcarbamoyloxy)thiorormiv XXIX it e. Isopropyl mercaptan do Allyl isflcyimate pl g liy y fl a oy -(ullylcarbamoyloxy)thloformi- In a e. 1 m d Propargyl isocyanate Methyltl-(dimethylcarbamoyl)-N-(propargyicarbamoyloxy)thioformim 8. B. Propyl mercaptan do Methyl iso yanate- Propgi l-(dim hyl arbumoyl)-N-(methy1carbamo 1ux )tm r rmim 8 G. d0 Al1yllsocyauate... Allyl 1-(dim 3thylflurbamoyl)-N-(ullylcarbamoyioxy)thioiormjmidate, figglofififiifi m "do Met y isocya at p op yl1-(dimethylcarbamoyi)-N-(meth lcnrbamo lox thiormmi.

m a e. Butyl mercaptan do do mg -(dimethylcarbamoyl)-N-(methylcarbamo lox )mmrmmim 8 e. ec-Butylmercaptgn m, .do -p ut yl l-(dimethylcarbamoyl)-N-(methy1earbamoyloxy)thioformlm D e. tert-Butyl mercaptan ..do .410 'QQ Y i hyl arbamoyl-)N (-methylcarbamoyloxy)thiot rmi- 1 do Ethyl isocyanate Meth 1l-(dimcthylcarbam0yl)-N-(ethylcarbamoyloxy)thlofoymimldate.

..do do uty 1-(d p y a bamovl)-N-(ethylcarbamo lox )thioiormimidate. Methyl mercaptan .do.... Isopropyl iso ya at Metp y -(d1m thylcarbamoyl-N-isopro ylcarbamo lox )tmor rmi.

m l1 e. Butyl mercaptan ..do.... d ut y t-(d et y carbflmayl)-N-(isopropylcarbamoyloxy)thioiormim a e. All 1 c i n do... Propylisocyanete. A1lyl1-(dimethylcarbamoyl)-N-(propylcarbamoylox )thiomrmimidate. Met h3g 2iei -gagtan "dd. Ally! isocyanate M hyl1-(dimethylcarbumoy1)-N-(allylcarbamoylox )thiorormimiaam. Butymemamamfln "A10" do Buty 1-(dimethylcarbamoyl)-N-(allylearbumoyloxy)thioformlmldate.

Allyl mercaptan .110 Propargyl iso yanate Ally l l{dimethylcurbamoyl)-N-(nropargylcnrhamo lox )thiorormi- WW- Vigil} m I TABLE I-Continued Mercaptan v Amine Isocyanate Product Methyl mercaptan Methylamlnedo..- Methyl l-(methylcarhamoyl)-N-(methylcarbamoylox )thiolormlmldate Do Butyhmlhe. do Methyl l-(btlty carbamoyl)-N-(methylcarbamoyloxy)ghioformlmidnto. Isoprpylme1capt8l'1. cyc opropy amm .d0 SIZDfO Dlgng-egie gpropy carbamoyl)-N-(methylcarbamoyloxy) I o o a e. Allyl mercaptan N,O-dimethylhydroxyl- Ethyl isocyanate. Allyl 1-(N-metlioxy-N-methylcarbamoyl)-N-(ethylcarbamoyloxy) amine. thioformirnidate. Ethylmercaptan.-. Isopropy amine Al y isocyanate Ethyl l-(isopropyl carbamoyl)-N-(allylcarbamoyloxy)thiol'ormimitlnte. Methyl mercaptan Ethylamine. Propargylisoeyanate Methyl 1-(ethylcarbamoyl)-N-(proparnylcarbamoyloxy)thloformimldate. Do Dlethylamlne Methyllsocyanate Methyl l-(diethylcarbamoyl)-N-(methylcarl amoyloxy)thiolomilmidato. Do Dusopropylamme ..d0 Methyl 1-(diisopropylcarbamoyl)-N-(methylcarhamoyloxy) thioformirnidate. D Azirldme. .410 Methyl 1(aZiridln0carb0nyl)-N-(methylcarbamoyloxy)thiol'ormimidntc. D() Hexahydroazepme do Methyl l-(hexahydrouzepinooarbonyD-N-(methylcarbamoyloxy) thioformimidate. Pyrrolidme ..d0 Methyl 1-(pyr10lidin0earbonyl)-N-(methylcarbamoyloxy) I thiol'ormimidate. Methylamlne. Allyllsqcyanate. Methyl l-(methylcarbamoyl)-N-(allylcarbamoyloxy)thioformlmldnte. N, O-dimethyl- Methyl tsoeyanate. i Methyl 1-(N-methoxy-N-methylcarbamoyl)-N-(methylcarbamoyloxy) hydroxylamine. thioformimidate. D N-methyl-N-ethylamme- Allyl lsocyanate. Methyl l-(N-methyl-N-ethylcarbamoyl)-N-(allylcarbamoyloxy) thioiormimidate. Do do ..d0 Methyl l-(N-methyl-N-ethy1carbamoy1)-N-(methylcarbamoyloxy) thloformimldate. Plperldme Allyl 1s oeyanate Ethyl l-(piperidinocarbonyl)-N-(allylcarbamoyloxy)thloforminidate.

do Butyl lsocyanate Ethyl l-(piperidinocerhonyl)-N-(butylcarbamuyloxy)thloformlmidute.

o Methyl lsccydnatev But-y] l-(piperidinoearbonyl)-N-(methylcarbamoyloxy) thioformimidate. Do do Butylrsocyanate Buty11-( iperidinocarbonyl)-N-(butylcarbamoyloxy)thlolormimidate. Methyl mercaptam. N-methyl-N-butylamine-- Methyl 1soeyanate Mettrl y} 1- N-mgthyl-N-butylcarbamoyl)-N-(methylcarbamoyloxy) 1o ormimi a. e.

EXAMPLE ll washed with ice water, and dried to give methyl l-(carbamoyl) N-hydroxythioformimidate, melting point l63l64 C.

Twenty-six and eight-tenths parts of methyl l-(car bamoyl)-N-hydroxythioformimidate, as obtained above, is treated as a suspension in 40 parts of acetone, containing k part of triethylenediamine, with 13 parts of methyl isocyanate. After the temperature of the reaction mass has begun to fall, the reaction mass is cooled to 0 C. and 36 parts of the product, methyl l- (carbamoyl)-N-(methylcarbamoyloxy)thioformimida te, is filtered off; it exhibits a melting point of i6 l-l 65 To asolution of 30 parts of concentrated aqueous ammonia in 200 parts of water is added at 25 C. enough diketene to givea stable pH of 7; 36l-parts of diketene (0.435 moles) is required. The resulting solution is then sparged with nitrogen and 30.5 parts of sodium nitrite is added, followed by the gradual addition of parts of 36 percent aqueous hydrochloric acid at 30 C. within 1 hour. A dark brown solution results, which is then treated at 30 C. within 1 hour with 31.5 parts of chlorine. After about it of the required amount of chlorine has been added, crystalv lization starts. When all of the chlorine has been added, Th compounds listed in Table are prepared by the the reaction mixture is agitated for another l hour. 40 procedures given in Example 1| using e mercaptans After cooling to filtration, washing'wilh ice and isocyanates listed in place of methyl 'mercaptan water and drying, there is obtained 44.5 parts ofcarmethyl isgcyanate.

TABLE II Mercaptan Isocyanate Product Ethyl mercaptan Methyl isocyanate Ethyl l-earbamoyl-N-(methylcarbamoyloxy)thlotormimldate. Ally] mercaptan .d0 Allyl l-carbamoyl-N-(methylcarbamoyloxy)thlotormimldate. But-zany] mercaptan.. Ethyl isocyanate... But-2-enyl l-carbamoyLN-(ethylcarbamoyloxy)thiotormimidate. Isopropyl mercaptan... Allyl isocyanate. Isopropyl 1-carbamoyl-N-(allylcarbamoyloxy)thioformimldate. Methyl mercaptan--. PIOEBIgYllSOCYSIlatB Methyl 1-carbamoy1-N-(profiargylcarbarnoyloxy)thiolormimidato. Propyl mercaptan Met yl xsocyanate. Propyl l-earbamoyl-N-(met ylcarbamoyloxy)thloformimldnte. Allyl mercaptan Allyhsocyanate Allyl l-carbamoyl-N-(allylcarbamoyloxy)thioformimidate. Isopropyl mereaptan. Methyl isocyanute. Isopropyl l-carbamoyl-N-(methylcarbamoyloxy)thlol'ormlmidate Butyl meroaptam Sec-butyl mercaptan. Tert-butyl mercaptan Butyl l-carbamoyl-N-(methylcarbamoyloxy)thiolormlmidatc. See-butyl l-earbamoyl-N-(methylcarbamoyloxy)thiotormimldate. l Tert-butyl l-earbamoyl-N-(methylearhamoyloxy)thiolormimldate.

o Methyl mercaptan Ethyl lsoeyanate, Methyl l-carbamoyl-N-(ethylcurbomayloxy)thloformimldate.

do Butyl l-curbamoyl-N-(ethylcarbamoyloxy)thioiormimidate. yl mercaptai Sopropyl isocyanate Methyl lcarbamoyl-N-(isopropylcarbarnoyloxy)thioformlmldato. Butyl mercaptan. do Butyl l-carbamoyl-N-(lsopropylcarbamoyloxy)thlolormimldate. Ally] mercaptan. .do Allyl1carbamoyl-N-(isopropylcarbamoyloxy)thiot'ormimidate.

Do n-Propyllsocyanate Allyl l-carbamoyl-N-(nropylcarbamoyloxy)thioformimidatc. Methyl mercaptan. Allyl isocyanate Methyl l-earbarnoyl-N- allylcarbamoyloxy)thiolormimldate. Butyl mereaptam ..sdo Butyl 1-carbamoyl-N-(allylcarbamoyloxylthioformimidate. Allylmercaptan Propargylisocyanate Allyl l-carbamoyl-N-(propargylcarbamoyloxy)thloformlmltlute.

, EXAMPLE lll To 690 parts of 26 percent aqueous dimethylamine Thirty-one parts of carbamoylformhydroxamoyl l 1600 Parts f water is added with agifation chloride, as obtained above, and 200 parts of water are dlketene at 200-30 a stable pH of 7 l d m 5 c. To this sus ension is added 17 parts of 65 i thlee f 9 of coo e p diketene IS required. In the resulting solution is then I dissolved 280 parts of sodium nitrite, followed by the percent aqueous sodium hydroxide solution to give gradual addition of 400 parts of 36 percem aqueous Stable P of Aflef agitation for an additional hydrochloric acid under a nitrogen atmosphere at 30 hour, the slurry is cooled to 0 C., the solids filtered off, C. The resulting 2-hydroxyimino-N,N-

bamoylforrnhydroxamoyl chloride, melting point l62-l63 C.

methyl mercaptan, followed by the gradual addition of 11 12 dimethylacetoacetamide, melting point l22-l24 C., dropwise at l-25 C. Stirring is continued for one crystallizes toward the end of the hydrochloric acid adhour after the completion of the addition. The inordition and can be isolated by cooling of the solution g nic Solids ar then removed by filtration and the and filtration. Without isolating the oxime, the reaction methyl Y y y mixture is treated within 60 minutes at 30 c. with 288 5 y)thioformimidate is recovered y removal of the parts of chlorine. At the beginning of the chlorination vent under du plessurethe oxime goes into solution and the reaction product begins to crystallize shortly thereafter. When all of the to the procedures of Example V using the chlorine has been added, the resulting reaction mixture thi f id t d ham 1 rid t d is agitated for k hour, followed by cooling to l0 C., blade 0 of m tliy l l-( i bam y l) N-l'lyd xyilifiifol filtration, washing with water and drying of the solids. mimidate and dimethy lcarbamoyl chloride.

The compounds of Table Ill are prepared according TABLE III N-hydroxythioformimidatc Carbamoyl chloride Product Methyl lcarhamoyl-Nhydroxythioformimidate Nallyl-N-methylcarbamoy] chloride Methyl 1carbamoyl-N-(N'allyl-N-methylcarbamoyloxy)thiol'ormimldate. D0. N-methyl-N-propargycarbamoyl chloride. Methyl l-carhamoylN-(N-methyl-N-proparttylcarbamoyloxy)thioformlmldate. D0. N-methyl-N-propylcarbamoyl chloride. Methyl 1-carbamoyl-N-(N-methyl-N-propylcarbamoyloxy)thloformtmidate. Do N-ethyl-N-methylcarbamoyl chloride Methyll-carbamoyl-N-(N-ethyl-N-methylcarbamoyloxy)thioformlmidate. Methyl 1metllylcarbamoyl-Nhydroxythioformimi- I )imethylcarbamoyl chloride Methyl l-(methylcarbnmoyl)N-(dimethylcurdate. bamoyloxy)thlolormlmidate. Methyl 1dimetliylcarbamoyl-N-hydroxythioformi- .....do Methyll-(dimethylcarbamoyl)N-(dlmethylcarmldate. bamoyloxy)thioformimldatc. Methyl 1cyclopentylcarbamoyl-N-hydroxythiofordo Methyl1(cyclopentylcarbamoyl)N-(dlmethylmimidatc. carbamoyloxy)thloiormimidate. Pmpyll-czirhamoyl-N-hydroxythlolormimidate ..d0 Proyll-carbamoyl-N-(dlmethylcurbumoylo y) thlolormimidate. EthyllcurbzwwylN-hydroxythioformimidatc d0 Ethyl l-carbamoyl-N-(dimothylcarbamoyloxylthioformimidate. Butyl1carbumoyl-Nhydroxythloiormimidate .do Butyl1earbamoyl-N-(dimethylcarbamoyloxy)- thioformlmidate.

There is obtained 561 parts of dimethylcarbamoyl- We claim: formhydroxamoyl chloride (93 percent yield based on 1- A process for chlorinating 2-hydroxdiketene) melting point 140-144 C. yiminoacetoacetamides of the formula EXAMPLE IV 0 o m To a solution of 79 parts of 2-hydroxyimino-N,N- dimethylacetoacetamide in 200 parts of water at 30 C. NOH R,

is gradually added within 45 to 60 minutes 36 parts of chlorine with good agitation. As the chlorination h i progresses the resulting reaction product crystallizes. 40 R is hydrogen, alkyl of one through four carbon When all of the chlorine has been added the reaction atoms, methoxy, or cycloalkyl of three through mixture is agitated at 30 C. for an additional '12 hour, five carbon atoms; and

during which time all of the chlorine has been com- R is hydrogen or alkyl of one through four carbon sumed and the reaction mixture has become colorless. atoms; With he P o iso that R; and R; can be Cooling to -l0 C., removal of the solids by filtration, tak n together and are alkylene of two through six and washing and drying the solids gives 69.7 parts of carbon atoms, and with the limitation lhal and dimethylcarbamoylformhydroxamoyl chloride, melting R8 never totaltmore than Seven carbon atoms; point to the corresponding hydroxamoyl chlorides comprising chlorinating the formula compound at a tempera- EXAMPLE V ture between about l0 C. and 75 C. in water, methanol, ethanol, isopropanol, their mixtures, or their mixtures with dimethylformamide, the chlorine being used in approximately stoichiometric amounts.

2. The process of claim 1 wherein the chlorination is carried out in water, at a temperature between about 20 C. and 50 C.

To a stirred suspension of 48 parts of 50 percent sodium hydride and mineral oil in 648 parts of tetrahydrofuran is added portion-wise over a one-hour period 114 parts of methyl l-(carbamoyD-N-hydrbxythioformimidate. The temperature is maintained at 20 to 30 C. After subsidence of hydrogen evolution, 107.5 parts of dimethylcarbamoyl chloride is added 

1. A CARBAMOYL CHLORIDE IN THE PRESENCE OF A BASE;
 2. PHOSGENE FOLLOWED BY REACTION WITH AN AMINE; OR
 2. The process of claim 1 wherein the chlorination is carried out in water, at a temperature between about 20* C. and 50* C.
 3. AN ISOCYANATE, OPTIONALLY IN THE PRESENCE OF A BASIC CATALYST; IN WATER OR ORGANIC SOLVENTS SUCH AS ACETONE, METHYLENE CHLORIDE, METHYL ETHYL KETONE, METHYL ISOBUTYL KETONE, DIMETHYLFORMAMIDE, DIMETHYLACETAMIDE, DIMETHYLSULFOXIDE, TETRAMETHYLUREA OR THEIR MIXTURES. 